The role of cytokines in polymyositis

OBJECTIVE: To investigate the effect of interferon-gamma (IFN gamma) on the adhesive interactions between human peripheral blood T cells and human skeletal muscle cells at various stages of muscle cell differentiation and maturation in vitro. METHODS: Human muscle cell cultures were established from normal muscle biopsy material, using the explant technique. T cells were studied for their capacity to adhere to IFN gamma-treated and untreated myoblasts and myotubes. The role of intercellular adhesion molecule type 1 (ICAM-1) in cell adhesion to muscle cells was examined in blocking studies, by enzyme-linked immunosorbent assay (ELISA), and by immunohistochemical staining using monoclonal antibodies (MAb). RESULTS: Treatment of muscle cells (myoblasts and myotubes) with IFN gamma resulted in a significant dose-dependent increase in the number of adherent T cells. Adhesion of T cells to muscle cells was significantly inhibited by MAb to ICAM-1 and to lymphocyte function-associated antigen type 1, but not by MAb to HLA-DR. There was no difference in the level of T cell adhesion to IFN gamma-treated allogeneic versus autologous muscle cells. By ELISA and immunohistochemical analysis, ICAM-1 expression on the surface of cultured human muscle cells was either absent or barely detectable, but was strongly induced by treatment of muscle cells with IFN gamma. CONCLUSION: Induction of cell adhesion molecules on muscle cells by IFN gamma may be an important mechanism for the localization of T cells in the affected muscles of patients with autoimmune myositis.